We investigated the effects of transient receptor potential M8 (TRPM8) channel on the proliferation and motility of androgen-independent prostate cancer PC-3 cells. After being permanently transfected with an empty vector and cDNA encoding the TRPM8 protein, cells were analysed for cell cycle distribution and motility using flow cytometry and scratch assay. Immunocytochemistry and Ca 2+ imaging analysis revealed the overexpression of functional TRPM8 channel on both endoplasmic reticulum and plasma membrane of PC-3-TRPM8 cells. Cell cycle distribution and scratch assay analysis revealed that TRPM8 induced cell cycle arrest at the G 0 /G 1 stage (P < 0.05) and facilitated the cell apoptosis induced by starvation (P < 0.05). Furthermore, TRPM8 inhibited the migration of PC-3-TRPM8 cells (P < 0.01) through the inactivation of focal-adhesion kinase. It appears that TRPM8 was not essential for the survival of PC-3 cells; however, the overexpression of TRPM8 had negative effects on the proliferation and migration of PC-3 cells. Thus, TRPM8 and its agonists may serve as important targets for the treatment of prostate cancer.
The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Twenty-four Sprague-Dawley male rats were randomly divided into three equal groups: eight had a sham operation, eight underwent bilateral nerve crushing with no further intervention and eight underwent bilateral nerve crushing with an immediate application of PRP on the site of injury. Erectile function was assessed by CN electrostimulation at 3 months and nerve regeneration was assessed by toluidine blue staining of CN and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate application of PRP, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the application of PRP had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibres than the injured control group but fewer than the sham group. These results show that the application of PRP to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that clinical application of PRP has potential repairing effect on CN and peripheral nerves.
Gene transfer of IGF-1 significantly increased erectile function in the STZ diabetic rats. These results suggest that in vivo gene transfer of IGF-1 might be a new therapeutic intervention for the treatment of erectile dysfunction (ED) in the STZ diabetic rats.
OBJECTIVETo explore the expression of transforming growth factor‐β1 (TGF‐β1) in penile tissue from rats after bilateral cavernosal nerve (CN) ablation, mimicking patients who have had no nerve‐sparing during prostatectomy.MATERIALS AND METHODSTen adult male rats (neurectomy group) had a bilateral CN resection aseptically under an operating microscope, with six sham‐operated rats as controls. Fifteen weeks after surgery an apomorphine test was used in all rats to assess penile erection. The penile specimens were then collected and prepared for detecting the expression of TGF‐β1 by reverse transcription‐polymerase chain reaction (RT‐PCR), western blot and immunohistochemistry, and for quantitative analysis of the ratio of smooth muscle to collagen fibres in the corpus cavernosum with confocal microscopy.RESULTSAll rats in the sham‐operated group but none after neurectomy had an erectile response after subcutaneous injection with apomorphine (100 µg/kg). Immunohistochemistry, RT‐PCR and western blot analyses showed a significantly higher expression of TGF‐β1 in the penile tissues after neurectomy than after sham surgery. Smooth muscle cells (fluorescing red) and collagen fibres (green autofluorescence) after paraformaldehyde fixation, were clearly identified by confocal microscopy. The fluorescence intensity expressed as the mean (sem) ratio of smooth muscle to collagen fibres in the corpus cavernosum after neurectomy was 0.265 (0.125), significantly lower than that in the sham‐operated group, at 0.760 (0.196) (P < 0.01).CONCLUSIONAn increased expression of TGF‐β1 in penile tissue which promotes the synthesis of collagen may be one of the important factors for the erectile dysfunction caused by bilateral CN ablation. Similar pathophysiological processes may occur in the corpus cavernosum of patients after radical prostatectomy.
EGF can improve bilateral epididymal sperm content and motility of the rat with surgically induced varicocele. The administration of EGF in combination with surgical repair is more effective than surgical repair or EGF administration alone. EGF might be useful for the treatment of infertility induced by varicocele.
Abundant evidence indicates that estrogens have an important role in the pathology of benign prostatic hyperplasia (BPH). To investigate the effect of 17beta-estradiol (E2) on the proliferation and apoptosis of prostatic smooth muscle cells (PSMCs), rat PSMCs were obtained and exposed to gradient concentrations (0.1-100 nmol/l) of E2 over varying amounts of time. The progression of cell cycle, cellular apoptosis, cyclin D1, Bcl-2 and Bax proteins were detected. The data show that the effect of E2 on rat PSMCs is bilateral: it promotes cell proliferation by enhancing the expression of cyclin D1, which accelerates G1 to S phase transition; on the other hand, it induces apoptosis of the cells by up-regulating the expression of Bax. We thus suggest that an increase in estrogen may exert a launching effect in the pathology of BPH.
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